Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells.
OBJECTIVE
The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), - innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity.


METHODS
Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg).


RESULTS
While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4(+)T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4(+)CD25(+) regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed.


CONCLUSIONS
The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity.
Tokita
Daisuke
D
Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh School of Medicine, Biomedical Science Tower, W1540, Pittsburgh, PA 15213, USA.
Sumpter
Tina L
TL
Raimondi
Giorgio
G
Zahorchak
Alan F
AF
Wang
Zhiliang
Z
Nakao
Atsunori
A
Mazariegos
George V
GV
Abe
Masanori
M
Thomson
Angus W
AW
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051940:B7-2 Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D000072100:Jagged-1 Protein; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072099:Serrate-Jagged Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D051940:B7-2 Antigen; D015704:CD4 Antigens; D002135:Calcium-Binding Proteins; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; D053645:Interleukin-2 Receptor alpha Subunit; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D018664:Interleukin-12